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Antiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-α receptor activation in a genetic model of absence epilepsy.
Neuropharmacology. 2013 Jun; 69:115-26.N

Abstract

N-palmitoylethanolamine (PEA), an endogenous fatty acid ethanolamide, plays a key role in the regulation of the inflammatory response and pain through, among others, activation of nuclear peroxisome proliferator-activated receptors (PPAR-α). Endogenous cannabinoids play a protective role in several central nervous system (CNS) disorders, particularly those associated with neuronal hyperexcitability. We investigated the effects of PEA and the role of PPAR-α in absence epilepsy using the WAG/Rij rat model. PEA, anandamide (AEA), a PPAR-α antagonist (GW6471) and a synthetic CB1 receptor antagonist/inverse agonist (SR141716) were administered to WAG/Rij rats in order to evaluate the effects on epileptic spike-wave discharges (SWDs) on EEG recordings. We studied also the effects of PEA co-administration with SR141716 and GW6471 and compared these effects with those of AEA to evaluate PEA mechanism of action and focusing on CB1 receptors and PPAR-α. Both PEA and AEA administration significantly decreased SWDs parameters (absence seizures). In contrast, GW6471 was devoid of effects while SR141716 had pro-absence effects. The co-administration of SR141716 with PEA or AEA completely blocked the anti-absence effects of these compounds. GW6471 antagonized PEA's effects whereas it did not modify AEA's effects. Furthermore, we have also measured PEA, AEA and 2-AG (2-arachidonoylglycerol) brain levels identifying significant differences between epileptic and control rats such as decreased PEA levels in both thalamus and cortex that might contribute to absence epilepsy. Our data demonstrate that PEA has anti-absence properties in the WAG/Rij rat model and that such properties depend on PPAR-α and indirect activation of CB1 receptors. This article is part of the Special Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'.

Authors+Show Affiliations

Department of Health Science, School of Medicine and Surgery, University Magna Graecia of Catanzaro, Viale Europa - Germaneto, 88100 Catanzaro, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23206503

Citation

Citraro, Rita, et al. "Antiepileptic Action of N-palmitoylethanolamine Through CB1 and PPAR-α Receptor Activation in a Genetic Model of Absence Epilepsy." Neuropharmacology, vol. 69, 2013, pp. 115-26.
Citraro R, Russo E, Scicchitano F, et al. Antiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-α receptor activation in a genetic model of absence epilepsy. Neuropharmacology. 2013;69:115-26.
Citraro, R., Russo, E., Scicchitano, F., van Rijn, C. M., Cosco, D., Avagliano, C., Russo, R., D'Agostino, G., Petrosino, S., Guida, F., Gatta, L., van Luijtelaar, G., Maione, S., Di Marzo, V., Calignano, A., & De Sarro, G. (2013). Antiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-α receptor activation in a genetic model of absence epilepsy. Neuropharmacology, 69, 115-26. https://doi.org/10.1016/j.neuropharm.2012.11.017
Citraro R, et al. Antiepileptic Action of N-palmitoylethanolamine Through CB1 and PPAR-α Receptor Activation in a Genetic Model of Absence Epilepsy. Neuropharmacology. 2013;69:115-26. PubMed PMID: 23206503.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-α receptor activation in a genetic model of absence epilepsy. AU - Citraro,Rita, AU - Russo,Emilio, AU - Scicchitano,Francesca, AU - van Rijn,Clementina M, AU - Cosco,Donato, AU - Avagliano,Carmen, AU - Russo,Roberto, AU - D'Agostino,Giuseppe, AU - Petrosino,Stefania, AU - Guida,Francesca, AU - Gatta,Luisa, AU - van Luijtelaar,Gilles, AU - Maione,Sabatino, AU - Di Marzo,Vincenzo, AU - Calignano,Antonio, AU - De Sarro,Giovambattista, Y1 - 2012/12/01/ PY - 2012/07/02/received PY - 2012/10/25/revised PY - 2012/11/22/accepted PY - 2012/12/5/entrez PY - 2012/12/5/pubmed PY - 2013/9/7/medline SP - 115 EP - 26 JF - Neuropharmacology JO - Neuropharmacology VL - 69 N2 - N-palmitoylethanolamine (PEA), an endogenous fatty acid ethanolamide, plays a key role in the regulation of the inflammatory response and pain through, among others, activation of nuclear peroxisome proliferator-activated receptors (PPAR-α). Endogenous cannabinoids play a protective role in several central nervous system (CNS) disorders, particularly those associated with neuronal hyperexcitability. We investigated the effects of PEA and the role of PPAR-α in absence epilepsy using the WAG/Rij rat model. PEA, anandamide (AEA), a PPAR-α antagonist (GW6471) and a synthetic CB1 receptor antagonist/inverse agonist (SR141716) were administered to WAG/Rij rats in order to evaluate the effects on epileptic spike-wave discharges (SWDs) on EEG recordings. We studied also the effects of PEA co-administration with SR141716 and GW6471 and compared these effects with those of AEA to evaluate PEA mechanism of action and focusing on CB1 receptors and PPAR-α. Both PEA and AEA administration significantly decreased SWDs parameters (absence seizures). In contrast, GW6471 was devoid of effects while SR141716 had pro-absence effects. The co-administration of SR141716 with PEA or AEA completely blocked the anti-absence effects of these compounds. GW6471 antagonized PEA's effects whereas it did not modify AEA's effects. Furthermore, we have also measured PEA, AEA and 2-AG (2-arachidonoylglycerol) brain levels identifying significant differences between epileptic and control rats such as decreased PEA levels in both thalamus and cortex that might contribute to absence epilepsy. Our data demonstrate that PEA has anti-absence properties in the WAG/Rij rat model and that such properties depend on PPAR-α and indirect activation of CB1 receptors. This article is part of the Special Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/23206503/Antiepileptic_action_of_N_palmitoylethanolamine_through_CB1_and_PPAR_α_receptor_activation_in_a_genetic_model_of_absence_epilepsy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(12)00564-3 DB - PRIME DP - Unbound Medicine ER -